In vitro activity of novel apramycin-dextran nanoparticles and free apramycin against selected Dutch and Pakistani Klebsiella pneumonia isolates
Nagina Atlas,
Bushra Uzair,
Julie Movellan,
Raquel Gracia,
Damien Dupin,
Iraida Loinaz,
Cornelus F. van Nostrum,
John P. Hays
Affiliations
Nagina Atlas
Dept. Biological Science, International Islamic University Islamabad, Pakistan; Utrecht Institute for Pharmaceutical Sciences, Dept. of Pharmaceutics, Utrecht University, Utrecht, the Netherlands
Bushra Uzair
Dept. Biological Science, International Islamic University Islamabad, Pakistan; Corresponding author.
Julie Movellan
CIDETEC, Basque Research and Technology Alliance (BRTA), Parque Científico y Tecnológico de Gipuzkoa, Miramon Pasealekua, 196, Donostia-San Sebastián 20014, Spain
Raquel Gracia
CIDETEC, Basque Research and Technology Alliance (BRTA), Parque Científico y Tecnológico de Gipuzkoa, Miramon Pasealekua, 196, Donostia-San Sebastián 20014, Spain
Damien Dupin
CIDETEC, Basque Research and Technology Alliance (BRTA), Parque Científico y Tecnológico de Gipuzkoa, Miramon Pasealekua, 196, Donostia-San Sebastián 20014, Spain
Iraida Loinaz
CIDETEC, Basque Research and Technology Alliance (BRTA), Parque Científico y Tecnológico de Gipuzkoa, Miramon Pasealekua, 196, Donostia-San Sebastián 20014, Spain
Cornelus F. van Nostrum
Utrecht Institute for Pharmaceutical Sciences, Dept. of Pharmaceutics, Utrecht University, Utrecht, the Netherlands
John P. Hays
Dept. Medical Microbiology & Infectious Diseases, Erasmus University Medical Centre (Erasmus MC), Rotterdam, the Netherlands; Corresponding author.
Klebsiella pneumoniae are bacteria associated with respiratory tract infections and are increasingly becoming resistant to antibiotics, including carbapenems. Apramycin is a veterinary antibiotic that may have the potential to be re-purposed for use in human health, for example, for the treatment of respiratory tract infections after coupling to inhalable nanoparticles. In the present study, the antibiotic apramycin was formulated with single chain polymeric nanoparticles and tested in free and formulated forms against a set of 13 Klebsiella pneumoniae isolates (from the Netherlands and Pakistan) expressing different aminoglycoside resistance phenotypes. Minimum Inhibitory Concentration, Time Kill Kinetics and biofilm experiments were performed providing evidence for the potential efficacy of apramycin and apramycin-based nanomedicines for the treatment of human Klebsiella pneumonia infections.